Department of Chemistry, University of California Davis, Davis, California 95616.
Foods for Health Institute, University of California Davis, Davis, California 95616; Department of Food Science and Technology, University of California Davis, Davis, California 95616.
Mol Cell Proteomics. 2019 Nov;18(11):2165-2177. doi: 10.1074/mcp.RA119.001648. Epub 2019 Aug 13.
Secretory Immunoglobulin A (SIgA) is central to mucosal immunity: represents one of the main immunological mechanisms of defense against the potential attack of pathogens. During lactation SIgA is produced by plasmablasts in the mammary gland and is present in breast milk, playing a vital role in the passive immunity of the newborn. Interestingly, the different components of SIgA are highly N-glycosylated, and these N-Glycans have an essential role in health maintenance. In this work, we performed a glycomic study to compare N-glycosylation of SIgA purified from mature breast milk and saliva, and plasma IgA from the same lactating participants. Our results revealed a greater diversity than previously reported, with 89 glycan compositions that may correspond to over 250 structures. Among these glycans, 54 glycan compositions were characterized as body-fluid specific. Most of these unique N-Glycan compositions identified in SIgA from mature milk and IgA from plasma were fucosylated and both fucosylated and sialylated species, whereas in salivary SIgA the unique structures were mainly undecorated complex N-Glycans. In addition, we evaluated the effect of delivery mode on (S)IgA glycosylation. Lactating participants who had given birth by vaginal delivery presented an increased proportion of high mannose and fucosylated glycans in salivary SIgA, and selected high mannose, fucosylated, sialylated, and both fucosylated and sialylated glycans in plasma IgA, indicating that the hormonal changes during vaginal delivery could affect plasma and saliva IgA. These results reveal the structural details that provide a new dimension to the roles of (S)IgA N-Glycans in different tissues, and especially in maternal and new-born protection and infant development. The design of optimal recombinant IgA molecules specifically targeted to protect mucosal surfaces will need to include this dimension of structural detail.
分泌型免疫球蛋白 A（SIgA）是黏膜免疫的核心：它是防御潜在病原体侵袭的主要免疫机制之一。在哺乳期，浆细胞在乳腺中产生 SIgA，并存在于母乳中，在新生儿的被动免疫中发挥着至关重要的作用。有趣的是，SIgA 的不同成分高度糖基化，这些 N-聚糖在维持健康方面起着至关重要的作用。在这项工作中，我们进行了糖组学研究，以比较从成熟母乳和唾液中纯化的 SIgA 以及来自同一哺乳期参与者的血浆 IgA 的 N-糖基化。我们的结果显示，与之前报道的相比，多样性更大，有 89 种聚糖组成，可能对应 250 多种结构。在这些糖中，有 54 种糖组成被认为是体液特异性的。在成熟乳中的 SIgA 和血浆 IgA 中鉴定出的这些独特的 N-聚糖组成物大多数是岩藻糖基化的，并且是岩藻糖基化和唾液酸化的，而在唾液 SIgA 中，独特的结构主要是未修饰的复杂 N-聚糖。此外，我们评估了分娩方式对（S）IgA 糖基化的影响。经阴道分娩的哺乳期参与者的唾液 SIgA 中高甘露糖和岩藻糖基化聚糖的比例增加，而血浆 IgA 中则选择了高甘露糖、岩藻糖基化、唾液酸化和岩藻糖基化和唾液酸化聚糖，表明阴道分娩期间的激素变化可能会影响血浆和唾液 IgA。这些结果揭示了结构细节，为（S）IgA N-聚糖在不同组织中的作用提供了新的维度，特别是在母婴保护和婴儿发育方面。设计专门针对保护黏膜表面的最佳重组 IgA 分子将需要包括这种结构细节的维度。
